20-3471064-T-G

Variant names:

• chr20-3471064-T-G
• rs758432510
• NM_139321.3:c.-44T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_139321.3(ATRN):​c.-44T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATRN NM_139321.3 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 20-3471064-T-G is Benign according to our data. Variant chr20-3471064-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3041871.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	NM_139321.3	MANE Select	c.-44T>G		5_prime_UTR	Exon 1 of 29	NP_647537.1	O75882-1
	ATRN	NM_001323332.2		c.-44T>G		5_prime_UTR	Exon 1 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.-44T>G		5_prime_UTR	Exon 1 of 25	NP_647538.1	O75882-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	ENST00000262919.10	TSL:5 MANE Select	c.-44T>G		5_prime_UTR	Exon 1 of 29	ENSP00000262919.5	O75882-1
	ATRN	ENST00000446916.2	TSL:1	c.-44T>G		upstream_gene	N/A	ENSP00000416587.2	O75882-2
	ATRN	ENST00000928835.1		c.-44T>G		upstream_gene	N/A	ENSP00000598894.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00175 AC: 2067 AN: 1179842 Hom.: 0 Cov.: 32 AF XY: 0.00162 AC XY: 943 AN XY: 583862

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00404 AC: 91 AN: 22524

American (AMR) AF: 0.00240 AC: 61 AN: 25402

Ashkenazi Jewish (ASJ) AF: 0.00596 AC: 112 AN: 18778

East Asian (EAS) AF: 0.00786 AC: 166 AN: 21116

South Asian (SAS) AF: 0.000209 AC: 15 AN: 71838

European-Finnish (FIN) AF: 0.00647 AC: 141 AN: 21794

Middle Eastern (MID) AF: 0.00275 AC: 9 AN: 3272

European-Non Finnish (NFE) AF: 0.00138 AC: 1306 AN: 948862

Other (OTH) AF: 0.00359 AC: 166 AN: 46256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 149290 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 72982

African (AFR) AF: 0.00 AC: 0 AN: 40808

American (AMR) AF: 0.00 AC: 0 AN: 15012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 4726

South Asian (SAS) AF: 0.00 AC: 0 AN: 4412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67316

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATRN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		1.6
PromoterAI		-0.14	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758432510; hg19: chr20-3451711;